Can PRP Injected Around Nerves Cause Serious Scar Tissue?

Published on Mar 21, 2023

Credit: Shutterstock

Anyone reading this blog knows I like to write about my daily experience. This week I got a call from a physician acting as an expert witness on a malpractice case against a physician who injected PRP into the scalene muscle. The argument made by the patient’s attorney is that since PRP can be pro-inflammatory, that injection caused severe scar tissue to form, which then caused thoracic outlet syndrome requiring surgery. Let’s dig into this idea and see if it holds water through a deep dive into the published literature.

The Phone Call

As an expert in orthobiologics, I frequently get random calls asking for advice about many things. That includes periodic calls from physicians or experts in malpractice cases involving orthobiologics. This call was from a physician expert who wanted to know what was published showing that injecting PRP into the muscles around nerves could lead to scar tissue.

The clinical scenario involved a physician injecting platelet-rich plasma (PRP) into the middle scalene using ultrasound guidance to treat neck pain. The patient eventually developed Thoracic Outlet Syndrome (TOS) that required surgery, and scar tissue was found around the brachial plexus that the patient claimed was due to the PRP procedure. Hence, a malpractice case was filed.

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The Basic Science Behind PRP and Nerves

PRP is made by centrifuging whole blood and concentrating platelets (1). These platelets release exosomes and vesicles containing growth factors that can aid healing. One of those released growth factors is NGF (Nerve Growth Factor), and it’s believed that through this growth factor as well as others like VEGF (which creates new blood vessels), PRP may be able to help nerve repair (2-6). In addition, PRP can limit experimental nerve injury in-vivo (17).

The Clinical Evidence that Injecting PRP Around Nerves is a Good or Bad Thing

Regrettably, a US National Library of Medicine search showed no publications on injecting PRP into the scalenes for use in the thoracic outlet or in treating the brachial plexus. I then shifted my search to other disorders where PRP had been used around nerves (perineural). This evidence comes primarily from two clinical applications: carpal tunnel syndrome and lumbar radiculopathy.

Carpal Tunnel Syndrome

There are eight randomized controlled trials published on platelet-rich plasma injections used to treat carpal tunnel syndrome, as shown in the infographic above (7-14). Seven were positive, and one showed no superiority in the short term compared to night splints. These trials combined treated 436 subjects, and no severe scarring episodes were reported.

Lumbar Radiculopathy

Based on a recent systematic review, 12 studies using platelet products (including PRP and platelet lysate) have been published on lumbar epidural use to treat radiculopathy (15). Three of these were RCTs, and the rest were case series. 267 patients were randomized, and no nerve scarring was reported in any of these studies. Considering the non-randomized studies for all platelet products (including our 470-patient platelet lysate study (18)) adds 991 patients in which no scarring was reported.

Other Perineural Applications

PRP has been injected around nerves in other settings as well. For example, Hassanien injected PRP perineural in patients with numbness due to diabetic peripheral neuropathy with good results and no reports of scarring (16). In these 60 randomized patients, no nerve scarring was reported.

Summary of the Published Data

No published data suggest that PRP injected around nerves causes scarring. Platelet products have been used around the nerves of significantly more than 1,000 patients who have had their results published in the literature without reported serious complications. That includes at least eleven randomized controlled trials.

The Orthobiologics Malpractice Space is Ramping Up

I have reported this a few times but will write it again. Based on the number of cases I have been contacted about these past few years, the medical malpractice industry is smelling blood in the proverbial water regarding orthobiologics. There are likely dozens of active malpractice and board cases. Some, like those against miracle cure chiropractic “stem cell” clinics, are pretty justified as, based on the chiro cases I have reviewed, actual bad decision-making created a bigger problem than needed to occur. However, significant nuisance cases like this one that can’t support the claim that a patient was somehow harmed just because PRP or another orthobiologic was injected are also common.

How can you protect yourself? Use a registry! While this physician got lucky that the published literature has shown safety for perineural injection since this injection, our data in the world’s largest orthobiologics registry showed that many years ago. The claim will still be made in court that since much of this published data wasn’t there when this medical provider performed this injection, its later publication doesn’t count. If this physician had been a Regenexx provider, data showing that scarring when platelet products are injected perineural isn’t a thing would be readily available. If you’re not part of the Regenexx network, use the excellent DataBiologics registry.

The upshot? I don’t know the name of the physician being sued for malpractice here, but I hope someone who knows this doctor gets this information. There is no credible data that injecting PRP around nerves causes scarring. More importantly, this is part of a more significant trend where interventional orthobiologics providers need to consider what they will do if they get tagged with a lawsuit like this one.

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References:

(1) Everts PA, Knape JT, Weibrich G, et al. Platelet-rich plasma and platelet gel: a review. J Extra Corpor Technol. 2006;38(2):174-187.

(2) Monje PV, Rendon S, Athauda G, Bates M, Wood PM, Bunge MB. Non-antagonistic relationship between mitogenic factors and cAMP in adult Schwann cell re-differentiation. Glia. 2009 Jul;57(9):947-61. doi: 10.1002/glia.20819. PMID: 19053056; PMCID: PMC2829776.

(3) Oudega M, Xu XM, Guénard V, Kleitman N, Bunge MB. A combination of insulin-like growth factor-I and platelet-derived growth factor enhances myelination but diminishes axonal regeneration into Schwann cell grafts in the adult rat spinal cord. Glia. 1997 Mar;19(3):247-58. doi: 10.1002/(sici)1098-1136(199703)19:3<247::aid-glia7>3.0.co;2-w. PMID: 9063731.

(4) Höke A, Sun HS, Gordon T, Zochodne DW. Do denervated peripheral nerve trunks become ischemic? The impact of chronic denervation on vasa nervorum. Exp Neurol. 2001 Dec;172(2):398-406. doi: 10.1006/exnr.2001.7808. PMID: 11716563.

(5) Kuffler DP, Reyes O, Sosa IJ, Santiago-Figueroa J. Neurological recovery across a 12-cm-long ulnar nerve gap repaired 3.25 years post trauma: case report. Neurosurgery. 2011 Dec;69(6):E1321-6. doi: 10.1227/NEU.0b013e31822a9fd2. PMID: 21712738.

(6) Zhu Y, Jin Z, Wang J, Chen S, Hu Y, Ren L, Wang Y, Song Q, Tian X, Xie F, Peng J, Peng N, Luo Y, Wang Y. Ultrasound-guided platelet-rich plasma injection and multimodality ultrasound examination of peripheral nerve crush injury. NPJ Regen Med. 2020 Nov 20;5(1):21. doi: 10.1038/s41536-020-00101-3. PMID: 33298932; PMCID: PMC7680141.

(7) Senna MK, Shaat RM, Ali AAA. Platelet-rich plasma in treatment of patients with idiopathic carpal tunnel syndrome. Clin Rheumatol. 2019 Dec;38(12):3643-3654. doi: 10.1007/s10067-019-04719-7. Epub 2019 Aug 16. PMID: 31420812.

(8) Shen YP, Li TY, Chou YC, Ho TY, Ke MJ, Chen LC, Wu YT. Comparison of perineural platelet-rich plasma and dextrose injections for moderate carpal tunnel syndrome: A prospective randomized, single-blind, head-to-head comparative trial. J Tissue Eng Regen Med. 2019 Nov;13(11):2009-2017. doi: 10.1002/term.2950. Epub 2019 Aug 20. PMID: 31368191.

(9) Shen YP, Li TY, Chou YC, Ho TY, Ke MJ, Chen LC, Wu YT. Comparison of perineural platelet-rich plasma and dextrose injections for moderate carpal tunnel syndrome: A prospective randomized, single-blind, head-to-head comparative trial. J Tissue Eng Regen Med. 2019 Nov;13(11):2009-2017. doi: 10.1002/term.2950. Epub 2019 Aug 20. PMID: 31368191.

(10) Wu YT, Ho TY, Chou YC, Ke MJ, Li TY, Huang GS, Chen LC. Six-month efficacy of platelet-rich plasma for carpal tunnel syndrome: A prospective randomized, single-blind controlled trial. Sci Rep. 2017 Dec;7(1):94. doi: 10.1038/s41598-017-00224-6. Epub 2017 Mar 7. PMID: 28273894; PMCID: PMC5427966.

(11) Malahias MA, Nikolaou VS, Johnson EO, Kaseta MK, Kazas ST, Babis GC. Platelet-rich plasma ultrasound-guided injection in the treatment of carpal tunnel syndrome: A placebo-controlled clinical study. J Tissue Eng Regen Med. 2018 Mar;12(3):e1480-e1488. doi: 10.1002/term.2566. Epub 2017 Dec 17. PMID: 28873284.

(12) Malahias MA, Nikolaou VS, Johnson EO, Kaseta MK, Kazas ST, Babis GC. Platelet-rich plasma ultrasound-guided injection in the treatment of carpal tunnel syndrome: A placebo-controlled clinical study. J Tissue Eng Regen Med. 2018 Mar;12(3):e1480-e1488. doi: 10.1002/term.2566. Epub 2017 Dec 17. PMID: 28873284.

(13) Malahias MA, Nikolaou VS, Johnson EO, Kaseta MK, Kazas ST, Babis GC. Platelet-rich plasma ultrasound-guided injection in the treatment of carpal tunnel syndrome: A placebo-controlled clinical study. J Tissue Eng Regen Med. 2018 Mar;12(3):e1480-e1488. doi: 10.1002/term.2566. Epub 2017 Dec 17. PMID: 28873284.

(14) Chang CY, Chen LC, Chou YC, Li TY, Ho TY, Wu YT. The Effectiveness of Platelet-Rich Plasma and Radial Extracorporeal Shock Wave Compared with Platelet-Rich Plasma in the Treatment of Moderate Carpal Tunnel Syndrome. Pain Med. 2020 Aug 1;21(8):1668-1675. doi: 10.1093/pm/pnz309. PMID: 31774510.

(15) Kubrova E, Martinez Alvarez GA, Her YF, Pagan-Rosado R, Qu W, D’Souza RS. Platelet Rich Plasma and Platelet-Related Products in the Treatment of Radiculopathy-A Systematic Review of the Literature. Biomedicines. 2022;10(11):2813. Published 2022 Nov 4. doi:10.3390/biomedicines10112813

(16) Hassanien M, Elawamy A, Kamel EZ, Khalifa WA, Abolfadl GM, Roushdy ASI, El Zohne RA, Makarem YS. Perineural Platelet-Rich Plasma for Diabetic Neuropathic Pain, Could It Make a Difference? Pain Med. 2020 Apr 1;21(4):757-765. doi: 10.1093/pm/pnz140. PMID: 31298289.

(17) Park GY, Kwon DR. Platelet-rich plasma limits the nerve injury caused by 10% dextrose in the rabbit median nerve. Muscle Nerve. 2014 Jan;49(1):56-60. doi: 10.1002/mus.23863. Epub 2013 Sep 20. PMID: 23558771.

(18) Centeno C., Markle J., Dodson E., Stemper I., Hyzy M., Williams C., Freeman M. The use of lumbar epidural injection of platelet lysate for treatment of radicular pain. J. Exp. Orthop. 2017;4:38. doi: 10.1186/s40634-017-0113-5.